Addition at Nitrogen

The diazines, pyridazine (p/faH 2.3), pyrimidine (1.3), and pyrazine (0.65) are essentially mono-basic substances, and considerably weaker, as bases, than pyridine (5.2). This reduction in basicity is believed to be largely a consequence of destabilisation of the mono-protonated cations due to a combination of inductive and mesomeric withdrawal by the second nitrogen atom. Secondary effects, however, determine the order of basicity for the three systems repulsion between the lone pairs on the two adjacent nitrogen atoms in 

Heterocyclic Chemistry 5th Edition John Joule and Keith Mills 2010 Blackwell F iblishing Ltd 

MA -Diprotonation is very much more difficult and has only been observed in very strongly acidic media. Of the trio, pyridazine (pA anca) -7.1) is the most difficult from which to generate a dication, probably due to the high energy associated with the juxtaposition of two immediately adjacent positively charged atoms, but pyrimidine (p/faH(2) -6.3) and pyrazine (pATanca) -6.6) are only marginally easier to doubly protonate. 

Substituents can affect basicity (and nucleophilicity) both inductively and mesomerically, but care is needed in the interpretation of pATaH changes, for example it is important to be sure which of the two nitrogens of the substituted azine is protonated (see also 14.1.1.2). 

The diazines react with alkyl halides to give mono-quaternary salts, though somewhat less readily than comparable pyridines. Dialkylation cannot be achieved with simple alkyl halides, however the more reactive trialkyloxonium tetrafluoroborates do convert aU three systems into di-quatemary salts.  

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Michael addition of electron-rich indoles to the phosphoryl acrylate 120, followed by ion-exchange, was shown to give the interesting phosphorylated indole derivatives 121 in good overall yields. On the other hand, addition at nitrogen was observed when electron deficient indoles were used as the substrates. The drawback of this route appears to be the long reaction times, typically one week <02S1351>. 

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